I recently wrote up some thoughts for a funder on how to accelerate coronavirus vaccine development (connected to 1Day Sooner's "Warp Speed 2.0" project with Institute for Progress supported by a planning grant from Schmidt Futures and some funding from FTX Future Fund). I figured they may be of interest to the EA community, so I've posted a version below (edits from original noted with <>).
- Summary: Next-gen coronavirus vaccines face an unclear market, confusing regulatory environment, and challenges conducting animal and human tests. Attractive solutions include surging regulatory capacity, creating pools of scarce resources (like lab animals and testing supplies), and making purchase commitments for products that meet specified targets (or prizes paying for studies of strong candidates). A White House “Warp Speed 2 Task Force” could coordinate Warp 2 teams at the FDA, BARDA, DoD, and the NIH to implement these and other solutions. Building GOP support is a key strategic priority. 1Day and IFP are currently working on developing a Warp 2 white paper, conference, regulatory advocacy for vaccine developers, and on lobbying campaigns focused on GOP and defense audiences.
- Obstacles to Developing Pan-Sarbeco and Intranasal Vaccines
- Unclear Timeline and Lack of Urgency: Given a lack of centralized direction, the standard assumption in the field seems to be that it will take 5-10 years or more to license a pan-sarbecovirus vaccine. This expectation creates compounding delays by decreasing urgency for each actor at each stage of development.
- Market Uncertainty: Any new product would be competing with existing licensed vaccines. Consumer demand for a new vaccine or booster is unclear (particularly given uncertain timing), and it’s additionally unclear whether a pan-sarbeco vaccine would be rolled out broadly or kept in reserve for future pandemics.
- Regulatory Uncertainty and Burden: The product specifications an intranasal or pan-sarbeco vaccine would have to meet are unclear as are the types of evidence required for approval (e.g. are there animal and in vitro study results sufficient for licensure for pan-sarbeco candidates?) Intranasal vaccine developers have reported that the non-human primate safety results required by the FDA prior to starting clinical testing are expensive and time-consuming.
- Animal Testing Availability: There is a shortage of appropriate lab specimens in which to test coronavirus vaccine candidates.
- Unclear Path to Test Human Efficacy: It has become essentially impossible to conduct clinical studies in people who have not developed COVID immunity via vaccination or infection, which makes human testing a challenge. Similarly, the potential need to conduct non-inferiority studies to establish efficacy could require any phase 3 study to be quite large and commercially difficult. Insofar as extended durability is a goal of next generation vaccine development, establishing that on a short time frame is also challenging.
- Complicated Funding Environment: To incentivize commercial developers to invest quickly and substantially would likely require guaranteeing a market of several billion dollars or more. The inflationary macroeconomic environment and evenly divided Senate make new spending on this level seem difficult to achieve, and it is unclear how to access unspent COVID relief funds for this purpose. Based on Pelosi's inability to pass a law reappropriating state funds from the American Rescue Plan to urgent COVID relief uses, accessing those funds seems difficult and complicated outside of congressional action.
- What Can the Federal Government Do?
- Create Warp Speed Task Force with Public Timeline: A Warp 2 program coordinated at the White House level with highly public, time-limited objectives would alter expectations of when vaccine authorization would be achieved and create clear lines of accountability. This coordinating committee could oversee “Warp 2” tasks forces within BARDA, the FDA, DOD, and the NIH that would execute policies like the recommendations below. Such a coordinating committee could potentially include previous administration officials affiliated with Warp Speed 1 for reasons of expertise, legitimacy, and GOP support.
- Increase Regulatory Capacity: The Warp Speed-era FDA worked around the clock to evaluate COVID vaccine submissions (i.e. literally overnight and weekend shifts, as much as a ~4x increase in staff capacity compared to normal working conditions). Creating an elite team within FDA staff (possibly paid at higher rates, possibly inviting ex-FDA alums to serve) to review coronavirus applications in shifts would accelerate and effectively subsidize development.
- Create Regulatory Certainty: FDA guidance on COVID vaccine boosters has significantly lagged behind development needs. While the WHO has sponsored two global consultations on pan-sarbecovirus vaccines, these have not yet translated into clear regulatory guidance on target product specifications, which the FDA ought to develop and provide. Additionally, the FDA should either internally conduct or fund regulatory science efforts to answer questions common to broad classes of coronavirus vaccine developers (e.g. the question “do intranasal COVID vaccine formulations create risks of brain damage?” currently requires most intranasal developer to conduct their own non-human primate tests but could potentially be broadly answered once and applied across all relevant candidates).
- Supply Scarce Resources to Developers: The Department of Defense and NIAID could develop centralized pools of scarce resources (such as humanized mice, appropriate non-human primates, human research volunteers, scarce lab supplies etc.) to rapidly and efficiently supply to eligible developers.
- Pull Funding Mechanisms: AMCs: Advanced purchase or advanced market commitments that specify target product characteristics and guarantee purchase could improve the commercial viability of intranasal and pan-sarbeco candidates. Insofar as new appropriations to do are prohibitively expensive, advance commitments from future federal purchasers (like CMS or the VA) could be explored as could multilateral coordination of purchase commitments with CAUKUS, G7, OECD, or other countries.
- Pull Funding Mechanisms: Prizes: An accelerated process to fund and approve clinical studies for promising candidates could be developed, including prizes to fund all or part of clinical studies or candidates that achieve pre-specified goals in earlier testing.
- Challenge Trials: For intranasal candidates aimed at providing sterilizing immunity and reducing viral shedding, COVID human challenge studies could be used to demonstrate efficacy in place of traditional phase 3 studies. This could be pursued within the U.S. or in collaboration with the UK (which has funded a working human challenge model for COVID). Alternately, a challenge model for common cold betacoronaviruses could be developed (as recommended by Anthony Fauci) to help test pan-sarbecovirus vaccine candidates, though not all such candidates would be appropriate for such a model.
- What Can <a Funder> Do?
- Ascertain mechanisms and feasibility of repurposing existing COVID funds for next-gen vaccine development
- Identify a champion in the administration for developing a Warp Speed 2 Task Force.
- Strategic Challenges
- GOP Support: A key attraction to a Warp Speed framework is its origination in a Republican administration. However, the GOP faces a largely low-trust, vaccine-skeptical constituency and tends to be opposed to government spending. This makes aggressive government vaccine development programs politically challenging for GOP leaders to support. Since the GOP is likely to control at least one house of congress after the 2022 elections, if a Warp Speed 2 will require significant funding, it will likely need GOP champions going forward. Moreover, in the long-term Warp Speed and market shaping approaches have great value but their viability may be dependent on enduring GOP support. The rise of the nationalist Trump wing of the party may create something of a blank policy canvas (or at least potential for policy heterodoxy), but the best way to access that opportunity may be mobilizing tribal sentiments that may involve negative partisanship against the left. That is, a Warp Speed 2 seen as imposed by GOP leaders on a reluctant Biden administration may have better prospects than a program originating in the executive branch that seeks to build bipartisan support.
- Size of Funding: Insofar as an advanced purchase commitment or advanced market commitment approach is desirable to create an incentive for commercial developers, that commitment will likely need to be at least several billion dollars to have any effect. To achieve this via new legislation seems quite difficult, though a multilateral international approach may help address this.
- Existing 1Day/IFP Plans
- White Paper: We are working with Rachel Glennerster, Chris Snyder, and Stanley Plotkin to produce a white paper (and likely eventually an academic article) laying out what advanced market commitments for a pan-sarbeco vaccine and intranasal COVID vaccines could look like and the financial and social gains it can produce. This could also be the basis for a target product profile to use with an AMC. Our goal is to finish this by September 1.
- <redacted because I haven't asked permission to share>
- GOP Advocacy: 1Day is developing a lobbying campaign for Warp Speed 2 and market shaping measures focused on building a network of GOP support. We are hoping to generate a letter from GOP legislators to Biden asking for a Warp 2 proposal by end of September. <We have published pro-Warp pieces in Quillette and City Journal aimed at a conservative audience and are hoping to publish in outlets like National Review and the Wall Street Journal in the next two months>
- Defense Advocacy: 1Day is developing a lobbying campaign focused on building capacity and interest in Warp 2 in the Department of Defense and among defense experts and focused legislators.
- Regulatory Science: 1Day seeks to collectively represent the regulatory interests of pan-sarbeco and intranasal COVID vaccine developers to achieve greater regulatory clarity on product targets, the proof needed for authorization, and safety testing required while also identifying ways to reduce regulatory burden and accelerate consideration of trial approval and authorization steps.
- Further Reading
